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Article: Potent neutralization of Hendra and Nipah viruses by human monoclonal antibodies

TitlePotent neutralization of Hendra and Nipah viruses by human monoclonal antibodies
Authors
Issue Date2006
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal Of Virology, 2006, v. 80 n. 2, p. 891-899 How to Cite?
AbstractHendra virus (HeV) and Nipah virus (NiV) are closely related emerging viruses comprising the Henipavirus genus of the Paramyxovirinae. Each has a broad species tropism and can cause disease with high mortality in both animal and human hosts. These viruses infect cells by a pH-independent membrane fusion event mediated by their attachment (G) and fusion (F) envelope glycoproteins (Envs). Seven Fabs, m101 to -7, were selected for their significant binding to a soluble form of Hendra G (sG) which was used as the antigen for panning of a large naïve human antibody library. The selected Fabs inhibited, to various degrees, cell fusion mediated by the HeV or NiV Envs and virus infection. The conversion of the most potent neutralizer of infectious HeV, Fab m101, to immunoglobulin G1 (IgG1) significantly increased its cell fusion inhibitory activity: the 50% inhibitory concentration was decreased more than 10-fold to approximately 1 μg/ml. The IgG1 m101 was also exceptionally potent in neutralizing infectious HeV; complete (100%) neutralization was achieved with 12.5 μg/ml, and 98% neutralization required only 1.6 μg/ml. The inhibition of fusion and infection correlated with binding of the Fabs to full-length G as measured by immunoprecipitation and less with binding to sG as measured by enzyme-linked immunosorbent assay and Biacore. m101 and m102 competed with the ephrin-B2, which we recently identified as a functional receptor for both HeV and NiV, indicating a possible mechanism of neutralization by these antibodies. The m101, m102, and m103 antibodies competed with each other, suggesting that they bind to overlapping epitopes which are distinct from the epitopes of m106 and m107. In an initial attempt to localize the epitopes of m101 and m102, we measured their binding to a panel of 11 G alanine-scanning mutants and identified two mutants, P185A and Q191 K192A, which significantly decreased binding to m101 and one, G183, which decreased binding of m102 to G. These results suggest that m101 to -7 are specific for HeV or NiV or both and exhibit various neutralizing activities; they are the first human monoclonal antibodies identified against these viruses and could be used for treatment, prophylaxis, and diagnosis and as research reagents and could aid in the development of vaccines. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/157431
ISSN
2014 Impact Factor: 4.439
2014 SCImago Journal Rankings: 2.692
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhu, Zen_US
dc.contributor.authorDimitrov, ASen_US
dc.contributor.authorBossart, KNen_US
dc.contributor.authorCrameri, Gen_US
dc.contributor.authorBishop, KAen_US
dc.contributor.authorChoudhry, Ven_US
dc.contributor.authorMungall, BAen_US
dc.contributor.authorFeng, YRen_US
dc.contributor.authorChoudhary, Aen_US
dc.contributor.authorZhang, MYen_US
dc.contributor.authorFeng, Yen_US
dc.contributor.authorWang, LFen_US
dc.contributor.authorXiao, Xen_US
dc.contributor.authorEaton, BTen_US
dc.contributor.authorBroder, CCen_US
dc.contributor.authorDimitrov, DSen_US
dc.date.accessioned2012-08-08T08:49:54Z-
dc.date.available2012-08-08T08:49:54Z-
dc.date.issued2006en_US
dc.identifier.citationJournal Of Virology, 2006, v. 80 n. 2, p. 891-899en_US
dc.identifier.issn0022-538Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/157431-
dc.description.abstractHendra virus (HeV) and Nipah virus (NiV) are closely related emerging viruses comprising the Henipavirus genus of the Paramyxovirinae. Each has a broad species tropism and can cause disease with high mortality in both animal and human hosts. These viruses infect cells by a pH-independent membrane fusion event mediated by their attachment (G) and fusion (F) envelope glycoproteins (Envs). Seven Fabs, m101 to -7, were selected for their significant binding to a soluble form of Hendra G (sG) which was used as the antigen for panning of a large naïve human antibody library. The selected Fabs inhibited, to various degrees, cell fusion mediated by the HeV or NiV Envs and virus infection. The conversion of the most potent neutralizer of infectious HeV, Fab m101, to immunoglobulin G1 (IgG1) significantly increased its cell fusion inhibitory activity: the 50% inhibitory concentration was decreased more than 10-fold to approximately 1 μg/ml. The IgG1 m101 was also exceptionally potent in neutralizing infectious HeV; complete (100%) neutralization was achieved with 12.5 μg/ml, and 98% neutralization required only 1.6 μg/ml. The inhibition of fusion and infection correlated with binding of the Fabs to full-length G as measured by immunoprecipitation and less with binding to sG as measured by enzyme-linked immunosorbent assay and Biacore. m101 and m102 competed with the ephrin-B2, which we recently identified as a functional receptor for both HeV and NiV, indicating a possible mechanism of neutralization by these antibodies. The m101, m102, and m103 antibodies competed with each other, suggesting that they bind to overlapping epitopes which are distinct from the epitopes of m106 and m107. In an initial attempt to localize the epitopes of m101 and m102, we measured their binding to a panel of 11 G alanine-scanning mutants and identified two mutants, P185A and Q191 K192A, which significantly decreased binding to m101 and one, G183, which decreased binding of m102 to G. These results suggest that m101 to -7 are specific for HeV or NiV or both and exhibit various neutralizing activities; they are the first human monoclonal antibodies identified against these viruses and could be used for treatment, prophylaxis, and diagnosis and as research reagents and could aid in the development of vaccines. Copyright © 2006, American Society for Microbiology. All Rights Reserved.en_US
dc.languageengen_US
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/en_US
dc.relation.ispartofJournal of Virologyen_US
dc.subject.meshAntibodies, Monoclonal - Biosynthesis - Immunologyen_US
dc.subject.meshAntibodies, Viral - Biosynthesis - Immunologyen_US
dc.subject.meshAntibody Specificityen_US
dc.subject.meshCross Reactionsen_US
dc.subject.meshDose-Response Relationship, Immunologicen_US
dc.subject.meshEpitopes - Immunologyen_US
dc.subject.meshGlycoproteins - Immunologyen_US
dc.subject.meshHendra Virus - Chemistry - Immunologyen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoglobulin Fab Fragments - Immunologyen_US
dc.subject.meshImmunoglobulin G - Immunologyen_US
dc.subject.meshNeutralization Testsen_US
dc.subject.meshNipah Virus - Immunologyen_US
dc.subject.meshPeptide Libraryen_US
dc.subject.meshSolubilityen_US
dc.subject.meshViral Envelope Proteins - Immunologyen_US
dc.titlePotent neutralization of Hendra and Nipah viruses by human monoclonal antibodiesen_US
dc.typeArticleen_US
dc.identifier.emailZhang, MY:zhangmy@hku.hken_US
dc.identifier.authorityZhang, MY=rp01409en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1128/JVI.80.2.891-899.2006en_US
dc.identifier.pmid16378991en_US
dc.identifier.scopuseid_2-s2.0-30344474011en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-30344474011&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume80en_US
dc.identifier.issue2en_US
dc.identifier.spage891en_US
dc.identifier.epage899en_US
dc.identifier.isiWOS:000234382900035-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridZhu, Z=11141735600en_US
dc.identifier.scopusauthoridDimitrov, AS=7101600999en_US
dc.identifier.scopusauthoridBossart, KN=6603229067en_US
dc.identifier.scopusauthoridCrameri, G=6507575662en_US
dc.identifier.scopusauthoridBishop, KA=8530897400en_US
dc.identifier.scopusauthoridChoudhry, V=8530897500en_US
dc.identifier.scopusauthoridMungall, BA=6603227375en_US
dc.identifier.scopusauthoridFeng, YR=7404543613en_US
dc.identifier.scopusauthoridChoudhary, A=8743351100en_US
dc.identifier.scopusauthoridZhang, MY=35316639300en_US
dc.identifier.scopusauthoridFeng, Y=7404544509en_US
dc.identifier.scopusauthoridWang, LF=23993130300en_US
dc.identifier.scopusauthoridXiao, X=7402168892en_US
dc.identifier.scopusauthoridEaton, BT=7102645943en_US
dc.identifier.scopusauthoridBroder, CC=7004376461en_US
dc.identifier.scopusauthoridDimitrov, DS=7202564539en_US

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